产品描述

Hydroxyurea 是一种抗肿瘤药，通过抑制核苷二磷酸还原酶而抑制DNA合成。

靶点（IC50 & Targe）

ribonucleoside diphosphate reductase

体外研究

hydroxyurea can inhibit HIV-1 replication. In vitro experiments have shown that the 90% inhibitory concentration (IC90) of hydroxyurea for laboratory strains of HIV-1 in activated PBMC is 0.4 mM. Hydroxyurea was also found to be synergistic with the nucleoside reverse transcriptase inhibitor didanosine and to inhibit HIV-1 replication in activated PBMC; this inhibition may be due to a reduction in deoxynucleoside triphosphate pool sizes. Hydroxyurea has been shown to sensitize didanosine-resistant mutants[1][2].hydroxyurea has demonstrated activity in the treatment of sickle cell anemia by increasing the production of fetal hemoglobin, which reduces hemolysis in patients with this disease. Hydroxyurea exerts its cytostatic effect through inhibition of ribonucleotide reductase—the rate-limiting enzyme responsible for the conversion of ribonucleotides to deoxyribonucleotides, which are essential for DNA synthesis. As a result, cellular division is arrested in the S phase[1].

细胞实验

Cell lines: Erythroid cells

Concentrations: 30 μM

Incubation Time: 96 h

Method: Erythroid cells obtained from peripheral blood of the same patients(Thirteen β-Thal/HbE patients are treated with hydroxyurea orally for 2 years at a starting dose of 5 mg/kg/day for 5 days/week with escalation to a maximum of 10 mg/kg/day) 1 year after they had stopped hydroxyurea treatment are treated with hydroxyurea in vitro.Treatment of cells performs in primary culture with 30 μM hydroxyurea for 96 hours.

(Only for Reference)

动物实验

Animal Models: Female athymic (nu/nu) nude mice(used for xenograft model)

Formulation: saline

Dosages: 1500 mg/kg

Administration: i.p.

(Only for Reference)

参考文献

[1] Lori F, et al. Clin Infect Dis. 2000, 30 Suppl 2:S193-7.

[2] Zala C, et al. Clin Infect Dis. 2000, Suppl 2:S143-50.

[3] Watanapokasin Y, et al. Exp Hematol. 2005, 33(12):1486-92.

[4] Boucher PD, et al. Gene Ther. 2002, 9(15):1023-30.